The long term objectives of this application are to establish the safety and efficacy of botulinum toxin type A for the treatment of achalasia. Achalasia is an uncommon swallowing disorder in which the lower esopageal sphincter fails to relax, resulting in dysphagia, regurgitation and weight loss. The present methods of treatment, pneumatic dilation or surgery, are generally effective in relieving symptoms in about 60%-90% of patients, but may be associated with significant morbidity. There is therefore a need for a safer and less invasive therapy for this condition, particularly in patients who are considered to be at high risk for the present forms of therapy (the elderly or those with comorbid problems). Intrasphincteric injection of botulinum toxin Type A in a dose of 80 units has shown promise as a safe, simple and effective therapy for patients with achalasia. Preliminary data has shown that at this dosage, about 40% of patients remain in remission one year after treatment. Based on reports in the skeletal muscle literature, it is hypothesized that increasing the dose will prolong the duration of response. The specific aims of this study are to compare the efficacy and safety of two different doses of botulinum toxin in the treatment of achalasia. The prinicipal measure of efficacy will be the duration of remission after initial tretment. We will also study the degree of initial improvement in symptoms as well as in objective measures of esophageal function. Toxicity will be assessed by clinical assessment as well as by objective tests. Induction of antibodies to botulinum toxin in response to either dose will also be studied. The study design consists of a controlled dose response trial in which a total of 56 patients with achalasia will be enrolled after clinical and objective evaluation of their esophageal function. Patients will be randomized to treatment to receive either BoTox 80 units or BoTox 160 units, injected endoscopically into the lower esophageal sphincter. One week later, the response to treatmernt will be assessed by changes in symptom score (scale 0 to 9), pharyngoesophagograms, esophageal manometry and scintigraphy. Symptoms and signs of toxicity, if any, will be carefully examined. Diaphragmatic function will be assessed at time of the second pharyngoesophagogram; to detect any weakness caused by possible diffusion of the toxin. The incidence of gastroesophageal reflux will be assessed by ambulatory 24 hour esophageal pH monitoring. Thereafter, patients will have followup clinical contacts every month and undergo esophageal scintigraphy at six monthly intervals for one year or until they relapse. Sera will be analyzed for antibodies to botulinum toxin before and six months after treatment.